At a Glance

HELLP syndrome is characterized by hemolysis (H), elevated liver enzymes (EL), and low platelets (LP). The incidence of HELLP syndrome among pregnant patients ranges from 0.1 to 0.2%. It develops in approximately 10-20% of patients with severe preeclampsia/eclampsia. Symptoms typically develop in the third trimester, but second trimester or postpartum disease is also possible. The most common clinical presentation is nausea-vomiting and epigastric and/or right upper quadrant pain. Approximately 85% of patients have hypertension and proteinuria. However, hypertension and/or proteinuria may be absent or mild in women with otherwise severe HELLP syndrome.

Notably, one of the major challenges of early detection of HELLP syndrome lies in its recognition, because the clinical presentation of HELLP is varied and patients frequently present with nonspecific symptoms or subtle signs. Diagnosis of the complete form of HELLP syndrome requires the presence of all three major elements (H+EL+LP). Partial or incomplete HELLP syndrome consists of only one or two components (H and/or EL and/or LP).

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The diagnosis of HELLP syndrome requires the presence of the laboratory abnormalities comprising its name. A series of recommended laboratory tests include:

Peripheral blood smear

Complete blood count (CBC) with platelet count

Serum aspartate aminotransferase (AST)

Serum alanine aminotransferase (ALT)

Serum lactate dehydrogenase (LDH)

Serum bilirubin

Obtaining these laboratory tests is highly recommended in all pregnant women with gestational hypertension, preeclampsia, or proteinuria with symptoms of preeclampsia.

Clinicians must be aware that 15-20% of patients with HELLP syndrome do not have antecedent hypertension or proteinuria. It has, therefore, been suggested to obtain a platelet count and liver enzymes in any pregnant women presenting with right upper quadrant or epigastric pain.

Authorities agree that hemolysis, liver dysfunction and thrombocytopenia must all be present for the diagnosis of complete HELLP syndrome. However, there is a lack of consensus regarding the degree of laboratory abnormalities for diagnosis of HELLP syndrome (e.g., what degree of elevation should be used to diagnose the syndrome).

Some investigators use AST, ALT, and LDH results above the upper reference interval, whereas others require elevations of at least two standard deviations above the mean for that laboratory to qualify for the diagnosis of HELLP syndrome. In addition, substantial inter-laboratory differences remain a major problem, in part, because of the different number of methods used.

The upper limit values vary wildly among laboratories, depending on the methods used. Therefore, clinicians should be familiar with the upper limits for these tests in their own laboratory when making the diagnosis of HELLP syndrome. The threshold used to establish abnormal tests can be tailored to the individual clinician’s laboratory reference values. The following values have been suggested as guides for helping make the diagnosis (See Table 1).

Table 1.

Test Results Indicative of the Disorder

Hemolysis

Elevated liver enzymes

Low platelets

Tennessee classification

LDH ≥ 600 IU/L or total bilirubin ≥1.2 mg/dL

AST ≥ 70 IU/L

≤100,000/mm3

Mississippi classification

Class 1

LDH ≥ 600 IU/L

AST or ALT ≥ 70IU/L

≤50,000/mm3

Class 2

LDH ≥ 600 IU/L

AST or ALT ≥ 70IU/L

≥50,000/mm3 ≤100,000/mm3

Class 3

LDH ≥ 600 IU/L

AST or ALT ≥ 40IU/L

≥100,000/mm3 ≤150,000/mm3

Partial/incomplete HELLP

One or more of the above laboratory abnormalities

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Elevate liver enzyme levels can be caused by many medications. Common medications include nonsteroidal anti-inflammatory drugs, antibiotics, antiepileptic drugs, inhibitors of hydroxymethylglutaryl-coenzyme A reductase, and antituberculosis drugs. In addition to medications, herbs and illicit drugs or substances may cause elevations in liver enzyme levels.

What Lab Results Are Absolutely Confirmatory?

The diagnosis of HELLP syndrome is made by H, EL and LP alone. The platelet count, a peripheral blood smear, AST, ALT, bilirubin, and LDH are required for the diagnosis of HELLP syndrome. The greater the laboratory abnormalities, the greater the clinician’s confidence in the diagnosis.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If peripheral blood smears are not routinely performed in clinical practice, elevated LDH and/or unconjugated bilirubin are considered sufficient evidence of hemolysis. However, an elevated LDH can also reflect hepatocyte destruction in addition to hemolysis. Evidence of hemolysis is also reflected by a declining hematocrit or hemoglobin and decreased haptoglobin.

It is essential to differentiate HELLP syndrome from acute fatty liver of pregnancy (AFLP). Additional laboratory tests can be requested to help the differential diagnosis. Women with AFLP are more likely than women with HELLP to present with prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), low glucose concentration, and increased creatinine concentration.

HELLP may be difficult to distinguish clinically from hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Coagulation studies, such as PT and aPTT and a peripheral blood smear, can be helpful to distinguish these disorders.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Serum lactate dehydrogenase

Hemolysis: LDH values will be increased by hemolysis. Red blood cells (RBCs) contain 150-300 times the LDH of plasma. Hemolysis may occur in vivo or invitro. In vitro hemolysis can be caused by transportation via pneumatic tube, vigorous mixing, or traumatic venipuncture. In vitro hemolysis should, therefore, be avoided, and a hemolyzed specimen is not acceptable.

Serum aspartate aminotransferase

Hemolysis: Hemolysis leads to a small increase in AST concentrations due to the high AST content of RBCs.